Takashi Mizowaki, M.D., Ph.D. Professor
We are developing innovative treatment approaches to eradicate cancers. As molecular biological approaches, we are analyzing how cancer cells acquire radioresistance in a tumor-specific microenvironment, hypoxia. We are especially focusing on the function of a transcription factor, hypoxia-inducible factor 1 (HIF-1), as a therapeutic target for radiosensitization. As physics engineering approaches, we are driving forward high-precision radiotherapy such as intensity-modulated radiotherapy, stereotactic irradiation and 4-D radiotherapy. Physicians, biologists, and experts in physics engineering who are interested in these translational approaches for cancer therapy are welcome.
Research and Education■ Biological approach
We aim to elucidate molecular mechanisms behind tumor radioresistance for the development of innovative strategies for cancer radiotherapy. We are analyzing functions of novel hypoxia-responsive genes in both radioresistance and local recurrence of tumors. Also, we are performing molecular imaging experiments to clarify localizations and dynamics of radioresistant cancer cells for refinement of precision radiotherapy in the future.
■ Physics and engineering approach
We are implementing basic researches and clinical applications of advanced high-precision radiotherapy such as intensity-modulated radiotherapy, stereotactic irradiation and image-guided radiotherapy. Our final goal is to achieve molecular tracking radiotherapy in which biological imaging and molecular biological approach are integrated into physics and engineering approach.
■ Clinical research
We have applied the radiobiological and medical physical research results to clinical practice. We developed innovative radiotherapy machine, Vero4DRT. We initiated the dynamic tumor-tracking radiotherapy using Vero4DRT with real-time monitoring in 2011 as first clinical use, and the dynamic tumor-tracking IMRT for pancreatic cancer in 2013. We are now conducting the multi-institutional clinical trial using the high precision irradiation technique.
Hypoxic cancer cells (green) distal to blood vessels (blue) are resistant to radiation damage (red)
Dynamic tracking irradiation with (Vero4DRT) high precision image-guided radiation therapy device, which was developed in conjunction
- Akimoto M, Nakamura M, Nakamura A, Mukumoto N, Kishi T, Goto Y, Mizowaki T, Hiraoka M. Inter- and intrafractional variation in the three-dimensional positions of pancreatic tumors due to respiration under real-time monitoring. International Journal of Radiation Oncology・Biology・ in press.
- Iramina H, Nakamura M, Iizuka Y, Mitsuyoshi T, Matsuo Y, Mizowaki T, Hiraoka M, and Kanno I. The accuracy of extracted target motion trajectories in four-dimensional cone-beam computed tomography for lung cancer patients. Radiotherapy and Oncology, 121, 46-51, 2016.
- Goto Y, Zeng L, Yeom CJ, Zhu Y, Morinibu A, Shinomiya K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Torii M, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H. UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha. Nature Communications, 6, 6153, 2015.
- Iizuka Y, Matsuo Y, Ishihara Y, Akimoto M, Tanabe H, Takayama K, Ueki N, Yokota K, Mizowaki T, Kokubo M, Hiraoka M. Dynamic tumor-tracking radiotherapy with real-time monitoring for liver tumors using a gimbal mounted linac. Radiotherapy and Oncology, 117, 496-500, 2015.
- Matsuo Y, Ueki N, Takayama K, Nakamura M, Miyabe Y, Ishihara Y, Mukumoto N, Yano S, Tanabe H, Kaneko S, Mizowaki T, Monzen H, Sawada A, Kokubo M, Hiraoka M. Evaluation of dynamic tumour tracking radiotherapy with real-time monitoring for lung tumours using a gimbal mounted linac. Radiotherapy and Oncology, 112, 360-364, 2014.
Radiation Oncology and Image-Applied TherapyProfessor：Takashi Mizowaki
Associate Professor：Yukinori Matsuo
Program-Specific Senior Lecturer： Mitsuhiro Nakamura・Yuki Miyabe
Assistant professor：Kenji Takayama・Michio Yoshimura・Katsuyuki Sakanaka・Yoko Goto
Program-Specific Assistant professor：Yusuke Iizuka・Tomohiro Katagiri・Yoshitomo Ishihara・Mami Akimoto